Diffusion Nuclear Magnetic Resonance (NMR) has been used for over 40 years. For isotropic systems, i.e. systems which have the same characteristics in all directions, the measure of a diffusion coefficient may be interpreted in terms of aggregate size, permeability of the medium through which the molecules are moving, and binding events occurring between the diffusing species and larger molecules or the porous matrix. The most common Diffusion NMR techniques rely on pairs of magnetic field gradient pulses to label the NMR radio frequency signal for displacements occurring during the time between the pulses. Diffusion NMR techniques and methods of analysis are not only applied in vitro but also in the context of medical magnetic resonance imaging (MRI) for the detection of pathological conditions such as ischemic stroke, demyelinization disorder, and tumours.
To distinguish whether a molecule is inside or outside a closed compartment is of outmost importance for a number of studies, e.g. the controlled release of an active substance or molecular transport in tissue and biological fluids. Permeability studies are therefore performed within the pharmaceutical sciences as well as the medical and biological departments.
In both imaging and non-imaging (spectral) experiments different non-invasive means are used to receive a specific contrast. Today these are often based on the diffusion coefficients. A common way is to rely on curve fittings on a simple diffusion experiment using the Kärger model (Kärger, J., H. Pfeifer, and W. Heink. 1988. Principles and applications of self-diffusion measurements by nuclear magnetic resonance. Adv. Magn. Reson. 12:1-89). A common diffusion experiment involves a diffusion encoding block. This is sometimes used also in MRI as a means of contrast.
The publication “Diffusion-diffusion correlation and exchange as a signature for local order and dynamics” by P. T. Callaghan et al, JOURNAL OF CHEMICAL PHYSICS VOLUME 120, NUMBER 8 22 FEB. 2004 discloses two-dimensional nuclear magnetic resonance experiments in the examination of local diffusional anisotropy under conditions of global isotropy. The methods, known as diffusion-diffusion correlation spectroscopy and diffusion exchange spectroscopy, employ successive pairs of magnetic field gradient pulses, with signal analysis using two-dimensional inverse Laplace transformation. However, a drawback with the method is that the proposed method is very time consuming due to the fact that the experiment, even in its most simple protocol, has to be repeated, in practice, at least 100 times. Where the purpose is a MRI image of human the time duration for the experiment would exceed what is viable.
In summary, up until now the currently available Diffusion NMR methods for estimating permeability exchange are either very time consuming (Callaghan) or rely on curve-fitting with only weak dependence between the estimated parameters and the information in the experimental data (Kärger). Other known methods that could be used to obtain the exchange times are invasive methods, such as observations of the diffusion of a marker molecule by means of light scattering, microscopy, absorption spectroscopy and X-ray. This is not only difficult to use in vivo due to the toxicology risks but one could never assure that the tissue and body fluids are unaffected by the introduced marker.
Hence, an improved method, system, computer-readable medium, and use would be advantageous.